Interleukin 12 receptor, beta 2 subunit explained

Interleukin 12 receptor, beta 2 subunit is a subunit of the interleukin 12 receptor. IL12RB2 is its human gene.^[1] IL12RB2 orthologs^[2] have been identified in all mammals for which complete genome data are available.

The protein encoded by this gene is a type I transmembrane protein identified as a subunit of the interleukin 12 receptor complex. The co-expression of this and IL12Rβ1 proteins was shown to lead to the formation of high-affinity IL12 binding sites and reconstitution of IL12 dependent signaling. While the IL12Rβ1 subunit is constitutively expressed, the expression of the IL12RB2 gene is up-regulated by interferon gamma. In Th1 cells, IL-12 signaling through the IL12 receptor leads to the phosphorylation of STAT4 and continued Th1 differentiation. The IL12Rβ2 subunit plays an important role in Th1 cell differentiation, since its absence leads to an abortive Th1 differentiation that has dysfunctional production of Th1 effector molecules.^[3] The up-regulation of this gene is found to be associated with a number of infectious diseases, such as Crohn's disease and leprosy, which is thought to contribute to the inflammatory response and host defense.^[1]

Interactions

Interleukin 12 receptor, beta 2 subunit has been shown to interact with Janus kinase 2.^[4]

RNA editing

The mRNA of this protein is subject to RNA editing.

Further reading

• Airoldi I, Guglielmino R, Carra G, etal . The interleukin-12 and interleukin-12 receptor system in normal and transformed human B lymphocytes. . Haematologica . 87 . 4 . 434–42 . 2002 . 11940489 .
• Chua AO, Chizzonite R, Desai BB, etal . Expression cloning of a human IL-12 receptor component. A new member of the cytokine receptor superfamily with strong homology to gp130. . J. Immunol. . 153 . 1 . 128–36 . 1994 . 10.4049/jimmunol.153.1.128 . 7911493 . 9211163 .
• Andrew SE, Goldberg YP, Kremer B, etal . The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. . Nat. Genet. . 4 . 4 . 398–403 . 1993 . 8401589 . 10.1038/ng0893-398 . 20645822 .
• Presky DH, Yang H, Minetti LJ, etal . A functional interleukin 12 receptor complex is composed of two beta-type cytokine receptor subunits. . Proc. Natl. Acad. Sci. U.S.A. . 93 . 24 . 14002–7 . 1997 . 8943050 . 10.1073/pnas.93.24.14002 . 19484 . 1996PNAS...9314002P . free .
• Zou J, Presky DH, Wu CY, Gubler U . Differential associations between the cytoplasmic regions of the interleukin-12 receptor subunits beta1 and beta2 and JAK kinases. . J. Biol. Chem. . 272 . 9 . 6073–7 . 1997 . 9038232 . 10.1074/jbc.272.9.6073 . free .
• Rogge L, Barberis-Maino L, Biffi M, etal . Selective expression of an interleukin-12 receptor component by human T helper 1 cells. . J. Exp. Med. . 185 . 5 . 825–31 . 1997 . 9120388 . 10.1084/jem.185.5.825 . 2196163 .
• Yamamoto K, Kobayashi H, Miura O, etal . Assignment of IL12RB1 and IL12RB2, interleukin-12 receptor beta 1 and beta 2 chains, to human chromosome 19 band p13.1 and chromosome 1 band p31.2, respectively, by in situ hybridization. . Cytogenet. Cell Genet. . 77 . 3–4 . 257–8 . 1997 . 9284929 . 10.1159/000134589 .
• Presky DH, Minetti LJ, Gillessen S, etal . Analysis of the multiple interactions between IL-12 and the high affinity IL-12 receptor complex . J. Immunol. . 160 . 5 . 2174–9 . 1998 . 10.4049/jimmunol.160.5.2174 . 9498755 . free .
• Morton SM, Bocaccio I, Depetris D, etal . Assignment of IL12RB2 to human chromosome 1p31.3→p31.2 between D1S230 and D1S198 . Cytogenet. Cell Genet. . 79 . 3–4 . 282–3 . 1998 . 9605872 . 10.1159/000134743 .
• Naeger LK, McKinney J, Salvekar A, Hoey T . Identification of a STAT4 binding site in the interleukin-12 receptor required for signaling . J. Biol. Chem. . 274 . 4 . 1875–8 . 1999 . 9890938 . 10.1074/jbc.274.4.1875 . free .
• Yamamoto K, Shibata F, Miura O, etal . Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus . Biochem. Biophys. Res. Commun. . 257 . 2 . 400–4 . 1999 . 10198225 . 10.1006/bbrc.1999.0479 .
• Yao BB, Niu P, Surowy CS, Faltynek CR . Direct interaction of STAT4 with the IL-12 receptor . Arch. Biochem. Biophys. . 368 . 1 . 147–55 . 1999 . 10415122 . 10.1006/abbi.1999.1302 .
• Matsui E, Kaneko H, Fukao T, etal . Mutations of the IL-12 receptor beta2 chain gene in atopic subjects . Biochem. Biophys. Res. Commun. . 266 . 2 . 551–5 . 2000 . 10600539 . 10.1006/bbrc.1999.1859 .
• van Rietschoten JG, Smits HH, Westland R, etal . Genomic organization of the human interleukin-12 receptor beta2-chain gene . Immunogenetics . 51 . 1 . 30–6 . 2000 . 10663559 . 10.1007/s002510050005 . 25756200 .
• van Rietschoten JG, Smits HH, van de Wetering D, etal . Silencer activity of NFATc2 in the interleukin-12 receptor beta 2 proximal promoter in human T helper cells . J. Biol. Chem. . 276 . 37 . 34509–16 . 2001 . 11438525 . 10.1074/jbc.M102536200 . free .
• Kim J, Uyemura K, Van Dyke MK, etal . A role for IL-12 receptor expression and signal transduction in host defense in leprosy . J. Immunol. . 167 . 2 . 779–86 . 2001 . 11441083 . 10.4049/jimmunol.167.2.779. free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Jones ML, Young JM, Huang QR, etal . Interleukin 12-augmented T cell proliferation of peripheral blood mononuclear cells from HIV-seropositive individuals is associated with interleukin 12 receptor beta 2 upregulation . AIDS Res. Hum. Retroviruses . 19 . 4 . 283–92 . 2003 . 12804004 . 10.1089/088922203764969483 .
• Yamamoto K, Yamaguchi M, Miyasaka N, Miura O . SOCS-3 inhibits IL-12-induced STAT4 activation by binding through its SH2 domain to the STAT4 docking site in the IL-12 receptor beta2 subunit . Biochem. Biophys. Res. Commun. . 310 . 4 . 1188–93 . 2003 . 14559241 . 10.1016/j.bbrc.2003.09.140 .

Notes and References

1. Web site: Entrez Gene: IL12RB2 interleukin 12 receptor, beta 2.
2. Web site: OrthoMaM phylogenetic marker: IL12RB2 coding sequence .
3. Koch MA, Thomas KR, Perdue NR, Smigiel KS, Srivastava S, Campbell DJ . T-bet(+) Treg Cells Undergo Abortive Th1 Cell Differentiation due to Impaired Expression of IL-12 Receptor β2. . Immunity . 37 . 3 . 501–10 . September 2012 . 22960221 . 3501343 . 10.1016/j.immuni.2012.05.031 .
4. Yamamoto . K . Shibata F . Miura O . Kamiyama R . Hirosawa S . Miyasaka N . Apr 1999 . Physical interaction between interleukin-12 receptor beta 2 subunit and Jak2 tyrosine kinase: Jak2 associates with cytoplasmic membrane-proximal region of interleukin-12 receptor beta 2 via amino-terminus . Biochem. Biophys. Res. Commun. . 257 . 2 . 400–4 . UNITED STATES. 0006-291X. 10198225 . 10.1006/bbrc.1999.0479 .